5VMM

Staphylococcus aureus IsdB bound to human hemoglobin

5VMM の概要

• エントリーDOI: 10.2210/pdb5vmm/pdb
• 分子名称: Hemoglobin subunit alpha, Hemoglobin subunit beta, Iron-regulated cell wall-anchored protein, ... (5 entities in total)
• 機能のキーワード: heme transfer, transport protein
• 由来する生物種: Staphylococcus aureus; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 174791.83

構造登録者

Bowden, C.F.,Chan, A.C.,Murphy, M.E. (登録日: 2017-04-27, 公開日: 2017-11-15, 最終更新日: 2023-10-04)

主引用文献

Bowden, C.F.M.,Chan, A.C.K.,Li, E.J.W.,Arrieta, A.L.,Eltis, L.D.,Murphy, M.E.P.
Structure-function analyses reveal key features in Staphylococcus aureus IsdB-associated unfolding of the heme-binding pocket of human hemoglobin.
J. Biol. Chem., 293:177-190, 2018

PubMed Abstract: IsdB is a receptor on the surface of the bacterial pathogen that extracts heme from hemoglobin (Hb) to enable growth on Hb as a sole iron source. IsdB is critically important both for growth on Hb and in infection models and is also highly up-regulated in blood, serum, and tissue infection models, indicating a key role of this receptor in bacterial virulence. However, structural information for IsdB is limited. We present here a crystal structure of a complex between human Hb and IsdB. In this complex, the α subunits of Hb are refolded with the heme displaced to the interface with IsdB. We also observe that atypical residues of Hb, His and His of αHb, coordinate to the heme iron, which is poised for transfer into the heme-binding pocket of IsdB. Moreover, the porphyrin ring interacts with IsdB residues Tyr and Tyr Previously, Tyr was observed to coordinate heme iron in an IsdB·heme complex structure. A Y440F/Y444F IsdB variant we produced was defective in heme transfer yet formed a stable complex with Hb ( = 6 ± 2 μm) in solution with spectroscopic features of the bis-His species observed in the crystal structure. Haptoglobin binds to a distinct site on Hb to inhibit heme transfer to IsdB and growth of , and a ternary complex of IsdB·Hb·Hp was observed. We propose a model for IsdB heme transfer from Hb that involves unfolding of Hb and heme iron ligand exchange.

PubMed: 29109153
DOI: 10.1074/jbc.M117.806562

実験手法

X-RAY DIFFRACTION (3.6 Å)